Colorectal Cancer Prevention

Cancer prevention and risk prediction form a key research theme within the Gastrointestinal Disease Orientated Academic Group and encompasses the Christie NHS Foundation Trust; The University of Manchester, Faculty of Medical and Human Sciences; South Manchester NHS Trusts; and Greater Manchester & Cheshire Cancer Research Network.

The Lead Investigator in this research programme is Andrew Renehan, Senior Lecturer in Cancer Studies and Surgery, supported by the clinical leads within the GI-DOG (Miss Sarah T O'Dwyer; Dr Mark P Saunders), the Clinical and Experimental Pharmacology (CEP) Group (Professor Caroline Dive) at the Paterson Institute for Cancer Research; and the North West Institute for BioHealth Informatics (NIBHI) (Dr Iain Buchan).

Research Overview

Colorectal cancer is the third commonest cancer in the UK with over 35,000 new cases per year. Unlike other common cancers, survival rates have improved only slightly in the past two decades as over a third of patients present with advanced disease - this underpins the importance of cancer prevention in this tumour group.

Primary Prevention

The primary prevention of colorectal cancer is more challenging, requires cross-disciplinary approaches, and lags behind research on screening. Epidemiological studies have demonstrated a number of lifestyle and dietary risk factors for colorectal cancer, among which are the following: red meat consumption, obesity, diets low in fruit and vegetables, and physical inactivity (which increase risk); aspirin and hormonal replacement therapy (which decrease risk).

Research at The Christie in Colorectal Cancer Primary Prevention

Recognising the importance of the worldwide obesity epidemic on health problems in general, Andrew Renehan leads a group focusing on translational research into the role of obesity and colorectal cancer. This is a new subgroup fully integrated within CEP, formed since January 2007 (see Renehan webpage on University site.

Given the complexities required to intervene in primary cancer prevention, the Colorectal Cancer and Obesity team has recently collaborated with the Centre for Research on Innovation and Competition, University of Manchester, on a proposal to use system (network) analyses to tease out areas of potential innovation and organisational need.

Secondary Prevention and Risk Prediction

The majority of colorectal cancers arise from benign precursors, known as polyps or adenomas. These are typically present in the large bowel for several years before they progress to invasive cancer and are asymptomatic. This period of "occult" disease offers a window of opportunity for the detection and removal of the tumour in a benign or early invasive state. This is the basis for colorectal cancer screening. There are broadly two modalities of colorectal cancer screening for the average-risk population: (i) faecal occult blood testing (FOBT) with subsequent colonoscopy in those with a positive test; or (ii) flexible sigmoidoscopy screening of the left colon, with identification of "at-risk" polyps - patients in whom polyps are classified as "high-risk" based mainly on size and histology criteria, undergo full large bowel examination by colonoscopy.

Research at the Christie in Colorectal Cancer Screening and Risk Prediction

The effectiveness of FOBT screening to reduce colorectal cancer mortality was demonstrated two decades ago in three large trials. The UK government are now implementing the findings of these trials and are rolling out the National Bowel Cancer Screening programme. Research projects linked to screening centres in the Greater Manchester area are in development, and will be linked with research activities at the Christie.

A parallel series of trials using "once-only" flexible sigmoidoscopy were commenced in several European countries in the late 1990s. The Christie participated in the largest of these - the MRC "Flexi-Scope" trial - lead locally by Miss Sarah O'Dwyer recruiting some 1800 participants from the South Manchester areas. This trial tested whether sigmoidoscopy can detect and remove benign polyps, and thus, have the potential to reduce colorectal cancer incidence as well as mortality. Research from the Christie (lead by Andrew Renehan) linked to this trial demonstrated that the measurement of insulin-like growth factors (IGFs) in the circulation has predictive potential for colorectal adenomas. We subsequently refined and quantified the relationship of circulating IGFs and tumour development through systematic review and meta-regression, and published several studies evaluating factors which may impact upon these predictive models through collaboration with The University of Aarhus, Denmark, and the MRC Human Nutrition Unit in Cambridge.

Beyond populations at average-risk of developing colorectal cancer, risk is mainly defined by family history and medical conditions with predisposition. An example of the latter is acromegaly, an endocrine disorder characterised by sustained hypersecretion of growth hormone, typically from a pituitary adenoma. In the mid-1990s, it was believed that this condition had a greater than 13-fold increase of colorectal cancer risk. Our research in collaboration with Professor Steve Shalet,Department of Endocrinology, The Christie demonstrated that this risk was exaggerated and that the true risk was more modest at 2-fold increase. We established a clinical protocol for colonoscopic screening in these patients, and also demonstrated that on average, the length of the large bowel is 20 per cent longer in acromegaly and is associated with more torturosity, making the performance of colonoscopy more challenging and potentially more hazardous.

An additional level of research in colorectal cancer screening is the use bio-mathematical modelling. Through collaboration with Dr Georg Luebeck, at the Fred Hutchinson Cancer Research Centre, Seattle, USA, we have shown the relative merits of a chemoprevention versus a genetic modulation approach to colorectal cancer prevention